1. Field of the Invention
The present invention relates generally to the field of molecular biology, stem cells, and differentiated cells. More particularly, it concerns programming of somatic cells and undifferentiated cells toward specific cell lineages, particularly endothelial cells and precursors of endothelial cells, such as endothelial progenitor cells.
2. Description of Related Art
Endothelial cells and precursors of endothelial cells have many potential therapeutic uses, including treatment of tissue ischemia—e.g., as occurs in atherosclerosis, myocardial infarction, and limb ischemia—repair of injured blood vessels, and bioengineering of grafts. Preliminary studies have shown that transplantation of endothelial progenitor cells (EPCs) may be useful in treating ischemia in patients with myocardial infarction or limb ischemia (Dzau et al., 2005). However, the clinical usefulness of EPCs obtained from patients is limited because patients in need of endothelial cell therapies often produce too few EPCs or EPCs that are functionally deficient.
In addition to such clinical applications, endothelial cells are in high demand for use in screening compounds and drugs for vascular toxicity, vascular permeability, and anti-cancer activity. However, primary endothelial cells have a finite proliferative potential due to their age, donor, and organ-type specific variations, all of which limit the ability to standardize endothelial cell culture protocols and to expand these cells in sufficient numbers for drug-screening purposes.
Endothelial cells may also be obtained from human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), both of which are capable of unlimited proliferation in vivo and retain their potential to differentiate into all somatic cell types. Differentiation of human ESCs or iPSCs into cells of endothelial lineage in vitro recapitulates normal in vivo development and includes stages of mesoderm induction and specification of angiogenic mesodermal precursors. The process requires the addition of specific inductive factors. Endothelial cells derived from human ESCs or iPSCs are functional in in vitro assays and capable of transplantation in vivo (Li et al., 2009). However, differentiation of endothelial cells from human ESCs or iPSCs is an inefficient process.
Therefore, there is a need for efficient production of endothelial cells and endothelial cell precursors for therapeutic and research uses.